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Updated: Oct 27, 2025
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer
Shujing Wang1,2,3, Hua Zhu1,2,3, Yingjie Li3,4
1Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China.
Background:
Death receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers.
Methods:
Balb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo. In the clinical study, patients with GI cancers planning to undergo surgical operation were enrolled and underwent 18F-FDG and 89Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope.
Results:
Preclinical studies showed that 89Zr-CTB006 PET could specifically detect DR5 expression levels in vivo. Twenty-one patients, including nine gastric cancers and 12 colorectal cancers, were enrolled. The biodistribution showed high uptake in the liver and spleen and low uptake in the brain, lung and muscle with an acceptable whole-body dosimetry of 0.349 mSv/MBq. Strikingly, the adrenal glands maintained stable high uptake over the entire examination in all patients. The tumor lesions showed different levels of uptake of 89Zr-CTB006 with a mean maximum standardized uptake value (SUVmax) of 6.63±3.29 (range 1.8-13.8). Tumor tissue was obtained from 18 patients, and 89Zr-CTB006 uptake in patients with RNAscope scores of 3-4 was significantly higher than that in patients with scores of 0-2. An SUVmax of 9.3 at 48 hours and 6.3 at 72 hours could be used to discriminate the DR5 expression status of tumors both with a sensitivity and specificity of 100% and 92.9%, respectively.
Conclusions:
89Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression.
Insights
Positron emission tomography (PET) with 89Zr-CTB006 can noninvasively detect Death receptor 5 (DR5) expression in gastrointestinal cancers. This imaging approach shows promise for screening patients who may benefit from DR5-targeted therapies.
Area of Science:
- Nuclear medicine and molecular imaging
- Oncology and cancer therapeutics
- Radiopharmaceutical development
Background:
- Death receptor 5 (DR5) is a key therapeutic target in cancer treatment.
- Clinical trials of DR5 agonists have faced challenges in demonstrating significant efficacy.
- Noninvasive imaging of DR5 expression is needed to guide patient selection for DR5-targeted therapies.
Purpose of the Study:
- To evaluate the feasibility of using 89Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression.
- To assess DR5 expression in preclinical cancer models and patients with gastrointestinal (GI) cancers.
Main Methods:
- Preclinical studies utilized micro-PET/CT imaging in xenograft models.
- A clinical study involved patients with GI cancers undergoing surgery, who received 18F-FDG and 89Zr-CTB006 PET/CT scans.
- Tumor tissues were analyzed using RNAscope to confirm DR5 expression levels.
Main Results:
- 89Zr-CTB006 PET demonstrated specific detection of DR5 expression in preclinical models.
- In 21 GI cancer patients, 89Zr-CTB006 PET showed favorable biodistribution and acceptable dosimetry.
- Tumor uptake of 89Zr-CTB006 correlated significantly with DR5 expression levels (RNAscope scores), with high sensitivity and specificity for discriminating expression status.
Conclusions:
- 89Zr-CTB006 PET/CT is effective in detecting DR5 expression in cancer patients.
- This imaging modality holds promise as a tool for screening patients with DR5 overexpression for targeted therapies.
